# US 5,352,790 A · Process for the preparation of 1.beta.-ethyl-1.alpha.-(hydroxymethyl)-1,2,3,4,6,7,12,12B.alpha.-octahyd ro-indolo[2,3,-A]quinolizine and novel intermediates > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,352,790 A - Document ID: US5352790A - Status: Granted - Kind: A - Application number: 07/877,172 - Filed: 1992-06-25 - Granted: 1994-10-04 - Earliest claimed: 1990-10-31 - Assignees: Richter Gedeon Vegeyszeti Gyar Rt. - Inventors: Janos Kreidl; Laszlo Czibula; Gyorgy Visky; Maria F. nee Kirjak; Ida D. nee Juhasz; Judit Brill, deceased; Katalin Nogradi - Web page: https://patentgrep.com/patent/US5352790A ## CPC - C07D 471/14: Ortho-condensed systems - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract The invention relates to a novel process for the preparation of (-) -1.beta.-ethyl-1.alpha.-(hydroxymethyl) - 1,2,3,4,6,7,12,12b.alpha.-octahydro-indolo[2,3-a]quinolizine of the formula (I) ##STR1## and to novel intermediates obtained in this process. The compound of the formula (I) prepared by the process of the invention possesses a peripheral vasodilator effect. ## Claims ### Claim 1 A process for the preparation of an optically active compound of the Formula (I) ##STR11## which comprises the steps of: (a) treating a compound of the Formula (II) ##STR12## with about an equimolar amount of formaldehyde or with a polymerized form thereof at a temperature near room temperature, to yield a racemic compound of the Formula (III) ##STR13## which is in dynamic equilibrium with the compound of the Formula (II) and which may optionally be isolated; (b) asymmetrically transforming the racemic compound of the Formula (III) with (-)-L-dibenzoyl-tartaric acid monohydrate, which is a resolving agent, wherein the compound of the Formula (III) is employed slightly in excess of the equivalent amount of the resolving compound to obtain a crystalline optically active salt of the Formula (IV) ##STR14## having a desired optical activity and an optically active salt of the Formula (V) ##STR15## having an undesired optical active dissolved in a mother liquor; and (c) separating the crystalline salt of the Formula (IV) from the mother liquor containing the salt of the Formula (V) and reducing the Formula (IV) salt to obtain the compound of the Formula (I) . ### Claim 2 (depends on 1) The process defined in claim 1, wherein according to step (a) the compound of the Formula (II) is reacted with paraformaldehyde, in a protic or dipolar aprotic solvent or in a mixture of these solvents. ### Claim 3 (depends on 1) The process defined in claim 1, wherein according to step (c), the reduction of the optically active salt of the Formula (IV) is carried out using either a chemical reducing agent or catalytic hydrogenation. ### Claim 4 A process for the preparation of an optically active compound of the Formula (I) ##STR16## which comprises the steps of: (a) asymmetrically transforming a compound of the Formula (II) ##STR17## at a temperature near room temperature with about an equimolar amount of formaldehyde or with a polymerized form thereof, and with (-)-L-dibenzoyl-tartaric acid monohydrate, which is a resolving agent, wherein the compound of the Formula (II) is employed slightly in excess of the equivalent amount of the resolving compound to obtain a crystalline optically active salt of the Formula (IV) ##STR18## having a desired optical activity and an optically active salt of the Formula (V) ##STR19## having an undesired optical activity dissolved in a mother liquor; and (b) separating the crystalline optically active salt of the Formula (IV) from the mother liquor containing the optically active salt of the Formula (V) and reducing the optically active Formula (IV) salt to obtain the compound of the Formula (I). ### Claim 5 (depends on 4) The process defined in claim 4, wherein according to step (a) the compound of the Formula (II) is reacted with paraformaldehyde and (-)-L-dibenzoyl tartaric acid monohydrate, in a protic or dipolar aprotic solvent or in a mixture of these solvents. ### Claim 6 (depends on 4) The process defined in claim 4 , wherein according to step (b), the reduction of the optically active salt of the Formula (IV) is carried out using either a chemical reducing agent or catalytic hydrogenation. ### Claim 7 A process for the preparation of an optically active compound of the Formula (I) ##STR20## which comprises the steps of: (a) asymmetrically transforming a racemic salt of the Formula ( IIa ) ##STR21## with about an equimolar amount of formaldehyde or with a polymerized form thereof, at a temperature near room temperature in the presence of a base to obtain a crystalline optically active salt of the Formula (IV) ##STR22## having a desired optical activity, and an optically active salt of the Formula (V) ##STR23## having an undesired optical activity dissolved in a mother liquor; and (b) separating the crystalline optically active salt of the Formula (IV) from the mother liquor containing the optically active salt of the Formula (V) and reducing the optically active Formula (IV) salt to obtain the compound of the Formula (I). ### Claim 8 (depends on 7) The process defined in claim 7, wherein according to step (a) the salt of the Formula (IIa) is asymmetrically transformed in a protic or dipolar aprotic solvent or in a mixture of these solvents using paraformaldehyde, and as the base triethylamine. ### Claim 9 (depends on 7) The process defined in claim 7, wherein according to step (a) the salt of the Formula (IIa) is asymmetrically transformed using as the base, the compound of the Formula (II) ##STR24## ### Claim 10 (depends on 7) The process defined in claim 7, wherein according to step (b), the reduction of the optically active salt of the Formula (IV) is carried out using either a chemical reducing agent or catalytic hydrogenation.